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New contrast media for deep insights

Researchers at the Helmholtz Zentrum München, in collaboration with colleagues from the Technical University of Munich (TUM), have developed two molecular sensors that allow them to see changes in the concentrations of the important signaling molecule calcium inside the body. Two publications in the journal ‘Analytical Chemistry’ describe the new options that could be put to use in various medical fields.

New contrast media for deep insights

When calcium binds to the hyperpolarized molecule, it changes the frequency at which the molecule resonates in MRI, similar to the way a tone sounds on a string instrument. Source: Barth van Rossum, Reprinted with permission from Mishra, A. et al.: Hyperpolarized Multi-Metal 13C‑Sensors for Magnetic Resonance Imaging. Analytical Chemistry, doi: 10.1021/acs.analchem.6b03039. Copyright 2016 American Chemical Society.

When physicians and scientists want to examine living tissue without opening up the body, they turn to modern imaging methods. The penetration depth is often limited, however, because after a certain distance, strong scattering of light causes a loss of signal.

Advances can be achieved by means of improved measuring instruments as well as corresponding responsive contrast agents, which translate biological processes into suitable signals that the scientists can read out. Under the supervision of Prof. Dr. Gil Gregor Westmeyer, a team at the Helmholtz Zentrum München with first authors Dr. Anurag Mishra and Dr. Giorgio Pariani has now described two new molecular sensors in the two papers. In the future, using these sensors in magnetic resonance imaging and optoacoustic imaging should make it possible to observe changes in the concentrations of the central signal molecule calcium deep inside the tissue.

In optoacoustic (or photoacoustic) imaging, laser pulses locally heat the target area, which causes a short-term expansion of the tissue leading to ultrasonic signals. The scientists then acquire these signals with an appropriate transducer and 'translate' them into three-dimensional images - without any radiation exposure. "It took a trick to make calcium molecules visible, which for example enter nerve cells during neuronal activity," explains study leader Westmeyer. "We were able to develop a molecule that selectively binds to calcium ions and then changes its color - its absorption spectrum," the scientist continues. "This molecule ensures that we always see a signal change on the screen when the calcium concentration changes."

The scientists also see great promise for their second molecule: This is also a binding partner for metal ions, but its structure and possible applications differ. "We use a somewhat more complex procedure for this approach," explains study leader Westmeyer. "The molecule that we use is labeled with C13 carbon atoms and is additionally hyperpolarized before use." The doctor uses this term to describe a procedure that is used for synchronization of nuclear spins, which then leads to especially strong signals in magnetic resonance imaging (MRI). When calcium binds to the hyperpolarized molecule, it changes the frequency at which the molecule resonates in MRI, similar to the way a tone sounds on a string instrument. Zinc, another biomedically important metal ion that, for example, is released along with insulin, generates a different tone. "The hyperpolarization of the new contrast media sensor allows us to increase the visibility of calcium and similar ions by a factor of ten to a hundred," Westmeyer explains the improvement. "We think that cardiovascular and neuroscientific research are two possible fields of application." 

Further Information

Professor Westmeyer is connected to both the Institute of Biological and Medical Imaging and the Institute of Developmental Genetics at the Helmholtz Zentrum München, as well as serving as a professor for molecular imaging at the Technical University of Munich (TUM). Both projects were financed by the Helmholtz ICEMED (Imaging and Curing Environmental Metabolic Diseases) Alliance.

Original Publications:
Mishra, A. et al. (2016): Hyperpolarized Multi-Metal 13C‑Sensors for Magnetic Resonance Imaging. Analytical Chemistry, doi: 10.1021/acs.analchem.6b03039

Mishra, A. et al. (2016): Near-Infrared Photoacoustic Imaging Probe Responsive to Calcium. Analytical Chemistry, doi: 10.1021/acs.analchem.6b03546

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute for Biological and Medical Imaging (IBMI) conducts research into in vivo imaging technologies for the biosciences. It develops systems, theories and methods of imaging and image reconstruction as well as animal models to test new technologies at the biological, preclinical and clinical level. The aim is to provide innovative tools for biomedical laboratories, for diagnosis and for the therapeutic monitoring of human diseases. 

Rising life expectancy is causing an increase in age-related, but also sociological and environmental, influences on the genes. The Institute of Developmental Genetics (IDG) examines these changes in genetic material. In the Mouse Genetics group, genetic animal models are developed to investigate various diseases. These models are analyzed in the Disease Modelling research group in order to identify gene functions and cell processes and evaluate the influence of the environment and aging processes. The group focuses on the examination of neurological and psychiatric diseases. 

Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 40,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, com-bined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany.